The study, a world first in comprehensive next-generation ‘mapping’ of an entire prostate cancer genome, was performed using the Irys® System from Bionano Genomics, Inc.
It uncovered ten times more large-scale DNA rearrangements than have previously been detected in prostate cancer. Large-scale rearrangements can include relocation of long stretches of DNA from one part of the genome to another, as well as deletions or insertions of DNA sequence at particular sites in the genome.
Prostate cancer is the most commonly diagnosed cancer in Australian men, and approximately 10% of men diagnosed with prostate cancer die from this disease.
Professor Vanessa Hayes, Head of Garvan’s Human Comparative and Prostate Cancer Genomics Laboratory, led the study.
Prof Hayes says, “Although we’ve been researching prostate cancer for many years, very little is understood about what drives these tumours.
“One of the biggest clinical challenges is distinguishing which cancers are going to spread and become life-threatening, and which patients could be spared harsh treatment they might not need. To have any hope of targeting treatment in this way, we first need to understand the genetic drivers of each individual tumour.
“From previous genome sequencing studies we know that prostate cancer has very few small genetic changes, but rather, is more likely driven by large complex rearrangements of DNA within the genome. This is different to most cancers, which are driven by small DNA mutations in a number of key genes,
“Until now, we had no way of observing these DNA rearrangements or structural variants in prostate cancer.”
The researchers used next-generation mapping technology in tandem with whole genome sequencing to uncover the most complete picture to date of the prostate cancer genomic landscape.
They studied a prostate tumour with a Gleason score of 7, the most commonly diagnosed form of prostate cancer, which is clinically highly unpredictable. They identified 85 large structural rearrangements, with over a third of these directly impacting on genes with known cancer-promoting potential.
“We identified 15 new potential drivers of prostate cancer,” says Prof Hayes.
“There is important synergy here with whole genome sequencing. We could not have done this with sequencing technology alone. Whole genome sequencing is invaluable in identifying small DNA mutations, but it may not detect when a gene has been completely deleted, transferred to another chromosome, or multiplied many times - which is what we see here. Using next-generation mapping, we saw huge amounts of large-scale rearrangements, and genome sequencing then enabled us to identify the genes affected by these rearrangements.”
“Several cancer-promoting genes were multiplied many times, increasing their potency, and potentially driving this prostate tumour.”
The study provides proof of principle that next-generation mapping can provide insights into prostate cancer, and has future clinical potential for determining the prognosis for an individual, diagnosing prostate cancer subtypes or selecting targeted therapies.
Prof Hayes’ team is the first in Australia to obtain next-generation mapping technology, and the first in the world to apply it to understanding an individual tumour.
“Whole genome sequencing opened a huge number of doors for our understanding of prostate cancer – next-generation mapping just doubled the number of doors,” says Prof Hayes.
“I believe that in the future this technology will complement next generation sequencing as a key to personalised medicine for prostate cancer.”
The study has just been published in the journal Oncotarget, and is available to read online.
This research was supported by the University of Sydney, The Petre Foundation, The Movember Foundation and Prostate Cancer Foundation of Australia.
Media enquiries: Meredith Ross (Garvan) – email@example.com – 0439 873258
Notes for editors
About Professor Vanessa Hayes
Prof Vanessa Hayes is Head of the Human Comparative and Prostate Cancer Genomics Laboratory in the Genomics and Epigenetics Division at the Garvan Institute of Medical Research. She also holds the Petre Chair of Prostate Cancer, a conjoint Professorship between Garvan and the University of Sydney. She is also an Honorary Professor of Medical Sciences, University of Limpopo, and Extraordinary Professor of Health Sciences at the University of Pretoria, South Africa; and Conjoint Professor of Medicine, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney.
This study was performed as part of the Prostate Cancer Metastasis (ProMis) program, an Australian-led international initiative.